Enzymes are highly selective catalysts, greatly accelerating both the rate and specificity of biochemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products.
Lipoxygenases are enzymes that catalyze the oxidation of polyunsaturated fatty acids. 15-lipoxygenase (15-LOX) is one such enzyme that catalyzes the oxidation of substrates such as linolenic acid, dihomo-gamma linolenic acid, eicosapentaenoic acid and arachidonic acid to the respective products 13-HODE, 15-HETrE, 15-OHEPA and 15-HETE.
15-LOX is responsible for the conversion of arachidonic acid to various biologically active metabolites including 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE). 15-HETE has been implicated in the pathogenesis of airway and allergic diseases such as asthma by contributing to bronchoconstriction, mucus secretion, and eosinophil migration. While 15-HETE has been implicated in proinflammatory reactions, other 15-LOX products, such as 15-OHEPA, 15-HETrE and 13-HODE, have been shown to have anti-inflammatory effects and may be medically useful.
Examples of potential medically useful indications for 15-LOX products, incorporated by reference, include, but are not limited to acne therapy (U.S. Pat. No. 8,293,790), erythema therapy (US patent application publication 2013/0101533), anti-microbials (US patent application publication 2012/0264705), fatty liver therapy (GB1300628.3), neuropathy therapy (WO2010/125330A1) and treatment for skin inflammation (U.S. Pat. No. 8,536,223).
The products of 15-LOX metabolism are unstable at room temperature and need to be stored at temperatures of −20° C. or less. Due to this instability, 15-LOX products have not been formulated for medical use. As shown below, an issue with these compounds is the tendency for the 15-LOX derived hydroxyl group to form fatty acid dimers by forming ester bonds with the carboxyl group of the fatty acid.

Because of the instability and dimer formation, their potential to be developed as a medicine has been a challenge. Pharmaceutically acceptable stable forms of 15-LOX products are described herein.